Yin Hsien-Sheng, Paterson Reay G, Wen Xiaolin, Lamb Robert A, Jardetzky Theodore S
Department of Biochemistry, Molecular Biology, and Cell Biology, Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208-3500, USA.
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9288-93. doi: 10.1073/pnas.0503989102. Epub 2005 Jun 17.
Class I viral fusion proteins share common mechanistic and structural features but little sequence similarity. Structural insights into the protein conformational changes associated with membrane fusion are based largely on studies of the influenza virus hemagglutinin in pre- and postfusion conformations. Here, we present the crystal structure of the secreted, uncleaved ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein, a member of the class I viral fusion protein group. The secreted human parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk regions. Unexpectedly, the structure reveals a six-helix bundle associated with the postfusion form of F, suggesting that the anchor-minus ectodomain adopts a conformation largely similar to the postfusion state. The transmembrane anchor domains of F may therefore profoundly influence the folding energetics that establish and maintain a metastable, prefusion state.
I类病毒融合蛋白具有共同的机制和结构特征，但序列相似性很低。对与膜融合相关的蛋白质构象变化的结构见解主要基于对处于融合前和融合后构象的流感病毒血凝素的研究。在此，我们展示了副粘病毒人类副流感病毒3融合（F）蛋白分泌型、未切割胞外域的晶体结构，F蛋白是I类病毒融合蛋白家族的成员。分泌型人类副流感病毒3 F蛋白形成一个具有独特头部、颈部和柄部区域的三聚体。出乎意料的是，该结构揭示了一个与F蛋白融合后形式相关的六螺旋束，这表明缺失跨膜锚定结构域的胞外域采用了一种与融合后状态基本相似的构象。因此，F蛋白的跨膜锚定结构域可能会深刻影响建立和维持亚稳态融合前状态的折叠能量。
